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Research paper thumbnail of Mitotane Therapy in Adrenocortical Cancer Induces CYP3A4 and Inhibits 5α-Reductase, Explaining the Need for Personalized Glucocorticoid and Androgen Replacement

The Journal of Clinical Endocrinology & Metabolism, 2013

Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane] is the first-line treatment f... more Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane] is the first-line treatment for metastatic adrenocortical carcinoma (ACC) and is also regularly used in the adjuvant setting after presumed complete removal of the primary tumor. Mitotane is considered an adrenolytic substance, but there is limited information on distinct effects on steroidogenesis. However, adrenal insufficiency and male hypogonadism are widely recognized side effects of mitotane treatment. Our objective was to define the impact of mitotane treatment on in vivo steroidogenesis in patients with ACC. At seven European specialist referral centers for adrenal tumors, we analyzed 24-h urine samples (n = 127) collected from patients with ACC before and during mitotane therapy in the adjuvant setting (n = 23) or for metastatic ACC (n = 104). Urinary steroid metabolite excretion was profiled by gas chromatography/mass spectrometry in comparison with healthy controls (n = 88). We found a sharp increase in the excretion of 6β-hydroxycortisol over cortisol (P < 0.001), indicative of a strong induction of the major drug-metabolizing enzyme cytochrome P450 3A4. The contribution of 6β-hydroxycortisol to total glucocorticoid metabolites increased from 2% (median, interquartile range 1-4%) to 56% (39-71%) during mitotane treatment. Furthermore, we documented strong inhibition of systemic 5α-reductase activity, indicated by a significant decrease in 5α-reduced steroids, including 5α-tetrahydrocortisol, 5α-tetrahydrocorticosterone, and androsterone (all P < 0.001). The degree of inhibition was similar to that in patients with inactivating 5α-reductase type 2 mutations (n = 23) and patients receiving finasteride (n = 5), but cluster analysis of steroid data revealed a pattern of inhibition distinct from these two groups. Longitudinal data showed rapid onset and long-lasting duration of the observed effects. Cytochrome P450 3A4 induction by mitotane results in rapid inactivation of more than 50% of administered hydrocortisone, explaining the need for doubling hydrocortisone replacement in mitotane-treated patients. Strong inhibition of 5α-reductase activity is in line with the clinical observation of relative inefficiency of testosterone replacement in mitotane-treated men, calling for replacement by 5α-reduced androgens.

Research paper thumbnail of but Has No Effect upon Fat Mass in Patients with Simple Obesity Low-Dose Growth Hormone Inhibits 11ß-Hydroxysteroid Dehydrogenase Type 1

Research paper thumbnail of reductase deficiency

Research paper thumbnail of Expression and Putative Role of 11b-Hydroxysteroid Dehydrogenase Isozymes within the Human Eye

PURPOSE. The human eye is an important target tissue for steroid hormones, and glucocorticoids ha... more PURPOSE. The human eye is an important target tissue for steroid hormones, and glucocorticoids have been implicated in the pathogenesis of ocular disease, including glaucoma. In peripheral tissues, corticosteroid hormone action is regulated at a prereceptor level through the activity of the 11b-hydroxy- steroid dehydrogenase (11b-HSD) isozymes: an oxo-reductase (11b-HSD1) that activates cortisol (F) from cortisone (E) and a dehydrogenase

Research paper thumbnail of Analysis of taxol and related diterpenoids from cell cultures by liquid chromatography-electrospray mass spectrometry

Journal of chromatography, Jan 2, 1993

Authentic taxanes (taxol, 10-deacetyltaxol, cephalomannine, 10-deacetylcephalomannine, baccatin I... more Authentic taxanes (taxol, 10-deacetyltaxol, cephalomannine, 10-deacetylcephalomannine, baccatin III) and extracts from cell cultures derived from various yew tree species have been analyzed by microbore high-performance liquid chromatography (HPLC)-electrospray mass spectrometry (ESMS). All gave excellent positive-ion ES spectra with dominant protonated molecules at low nozzle-to-skimmer bias value (45 V). By increasing the voltage value to 85 V, fragmentation increased and structurally informative spectra were obtained. The fragments found were both of the C-13 side-chain and of the taxane ring, so their analysis gave important information about the taxane structure and any chemical modifications at different positions of the molecule. When tandem MS was used (argon gas, 25 eV collision energy), fragments similar to those obtained from collision-induced dissociation in the source were detected. The cell culture extracts were analyzed by microbore HPLC-ESMS and excellent spectra wer...

Research paper thumbnail of Steroid production and excretion by the pregnant mouse, particularly in relation to pregnancies with fetuses deficient in Δ7-sterol reductase (Dhcr7), the enzyme associated with Smith–Lemli–Opitz syndrome

Research paper thumbnail of Biochemical and physiological improvement in a mouse model of Smith–Lemli–Opitz syndrome (SLOS) following gene transfer with AAV vectors

Molecular Genetics and Metabolism Reports, 2014

Smith-Lemli-Opitz syndrome (SLOS) is an inborn error of cholesterol synthesis resulting from a de... more Smith-Lemli-Opitz syndrome (SLOS) is an inborn error of cholesterol synthesis resulting from a defect in 7-dehydrocholesterol reductase (DHCR7), the enzyme that produces cholesterol from its immediate precursor 7-dehydrocholesterol. Current therapy employing dietary cholesterol is inadequate. As SLOS is caused by a defect in a single gene, restoring enzyme functionality through gene therapy may be a direct approach for treating this debilitating disorder. In the present study, we first packaged a human DHCR7 construct into adeno-associated virus (AAV) vectors having either type-2 (AAV2) or type-8 (AAV2/8) capsid, and administered treatment to juvenile mice. While a positive response (assessed by increases in serum and liver cholesterol) was seen in both groups, the improvement was greater in the AAV2/8-DHCR7 treated mice. Newborn mice were then treated with AAV2/8-DHCR7 and these mice, compared to mice treated as juveniles, showed higher DHCR7 mRNA expression in liver and a greater improvement in serum and liver cholesterol levels. Systemic treatment did not affect brain cholesterol in any of the experimental groups. Both juvenile and newborn treatments with AAV2/8-DHCR7 resulted in increased rates of weight gain indicating that gene transfer had a positive physiological effect.

Research paper thumbnail of Longitudinal changes in glucocorticoid metabolism are associated with later development of adverse metabolic phenotype

European journal of endocrinology / European Federation of Endocrine Societies, 2014

Dysregulation of enzymes that control local tissue steroid metabolism has been implicated in the ... more Dysregulation of enzymes that control local tissue steroid metabolism has been implicated in the pathogenesis of obesity and insulin resistance; however, longitudinal changes in glucocorticoid metabolism have not been investigated. This study was performed to evaluate the role of glucocorticoid metabolism in the development of insulin resistance and obesity and to identify biomarkers for future development of metabolic disease. This was a prospective longitudinal observation study conducted over 5 years. A 24-h collection was used to serially analyze urinary glucocorticoid and mineralocorticoid metabolites in 57 obese and overweight patients with no prior diagnosis of diabetes mellitus, recruited from the community. Baseline higher 5α-reductase (5αR) activity, but not 11β-hydroxysteroid dehydrogenase type 1 activity, was predictive of increased fasting insulin at final visit (11.4 compared with 7.4 mU/l in subjects with lower 5αR activity, P<0.05), area under the curve insulin re...

Research paper thumbnail of Identification of a duplicated P450 side-chain cleavage enzyme (zCyp11a2) defines initiation and maintenance of steroidogenesis in zebrafish

Endocrine Abstracts, 2013

Research paper thumbnail of The zebrafish ferredoxin orthologue Fdx1b is essential for the redox regulation of interrenal steroidogenesis in larvae and adult fish

Endocrine Abstracts, 2013

Research paper thumbnail of Mutants of 11b-Hydroxysteroid Dehydrogenase (11-HSD2) With Partial Activity Improved Correlations Between Genotype and Biochemical Phenotype in Apparent Mineralocorticoid Excess

Mutations in the kidney isozyme of human 11-hydroxysteroid dehydrogenase (11-HSD2) cause apparent... more Mutations in the kidney isozyme of human 11-hydroxysteroid dehydrogenase (11-HSD2) cause apparent mineralocorticoid excess, an autosomal recessive form of familial hypertension. We studied 4 patients with AME, identifying 4 novel and 3 previously reported mutations in the HSD11B2 (HSD11K) gene. Point mutations causing amino acid substitutions were introduced into a pCMV5/11HSD2 expression construct and expressed in mammalian CHOP cells. Mutations

Research paper thumbnail of 232. Gene Therapy for Deficient Cholesterol Synthesis in a Mouse Model of SLOS

Molecular Therapy, 2005

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder, characterized by dysmorphol... more Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder, characterized by dysmorphology and mental retardation. It is a relatively high frequency inherited disease (1:20,000-1:40,000). The cause is a relative inactivity of 7-dehydrocholesterol-Δ7 -reductase (DHCR7), the terminal enzyme in cholesterol (C) synthesis. Affected individuals have low levels of C in blood and tissues and an accumulation of 7-dehydrocholesterol (7-DHC) and its isomer

Research paper thumbnail of Cortisol Metabolism in Human Obesity: Impaired Cortisone3Cortisol Conversion in Subjects with Central Adiposity

For a given body mass index (BMI), mortality is higher in patients with central compared to gener... more For a given body mass index (BMI), mortality is higher in patients with central compared to generalized obesity. Glucocorticoids play an important role in determining body fat distribution, but circulating cortisol concentrations are reported to be normal in obese patients. Our recent studies show enhanced conversion of inactive cortisone (E) to active cortisol (F) through the expression of 11b-hydroxysteroid dehydrogenase

Research paper thumbnail of Confirming testosterone administration by isotope ratio mass spectrometric analysis of urinary androstanediols

Research paper thumbnail of Gas chromatography/mass spectrometry (GC/MS) remains a pre-eminent discovery tool in clinical steroid investigations even in the era of fast liquid chromatography tandem mass spectrometry (LC/MS/MS)

Journal of Steroid Biochemistry and Molecular Biology, 2010

Research paper thumbnail of Quantitation of cortisol and related 3-oxo-4-ene steroids in urine using gas chromatography/mass spectrometry with stable isotope-labeled internal standards

Research paper thumbnail of Comparative Rates of Androgen Production and Metabolism in Caucasian and Chinese Subjects

Clinically apparent prostate cancer occurs more commonly among Caucasians living in Western count... more Clinically apparent prostate cancer occurs more commonly among Caucasians living in Western countries than in Chinese in the Far East. Prior studies demonstrated diminished facial and body hair and lower levels of plasma 3a-androstanediol glucuronide and andros- terone glucuronide in Chinese than in Caucasian men. Based upon these findings, investigators postulated that Chinese men could have diminished 5a-reductase activity with

Research paper thumbnail of A Genetic Defect Resulting in Mild Low-Renin Hypertension

Proceedings of The National Academy of Sciences, 1998

Severe low-renin hypertension has few known causes. Apparent mineralocorticoid excess (AME) is a ... more Severe low-renin hypertension has few known causes. Apparent mineralocorticoid excess (AME) is a genetic disorder that results in severe juvenile low-renin hypertension, hyporeninemia, hypoaldosteronemia, hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. In 1995, it was shown that mutations in the gene (HSD11B2) encoding the 11beta -hydroxysteroid dehydrogenase type 2 enzyme (11beta -HSD2)

Research paper thumbnail of Hair and skin sterols in normal mice and those with deficient dehydrosterol reductase (DHCR7), the enzyme associated with Smith-Lemli-Opitz syndrome

The Journal of Steroid Biochemistry and Molecular Biology, 2010

Research paper thumbnail of Human Δ4-3-oxosteroid 5β-reductase (AKR1D1) deficiency and steroid metabolism

Research paper thumbnail of Mitotane Therapy in Adrenocortical Cancer Induces CYP3A4 and Inhibits 5α-Reductase, Explaining the Need for Personalized Glucocorticoid and Androgen Replacement

The Journal of Clinical Endocrinology & Metabolism, 2013

Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane] is the first-line treatment f... more Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane] is the first-line treatment for metastatic adrenocortical carcinoma (ACC) and is also regularly used in the adjuvant setting after presumed complete removal of the primary tumor. Mitotane is considered an adrenolytic substance, but there is limited information on distinct effects on steroidogenesis. However, adrenal insufficiency and male hypogonadism are widely recognized side effects of mitotane treatment. Our objective was to define the impact of mitotane treatment on in vivo steroidogenesis in patients with ACC. At seven European specialist referral centers for adrenal tumors, we analyzed 24-h urine samples (n = 127) collected from patients with ACC before and during mitotane therapy in the adjuvant setting (n = 23) or for metastatic ACC (n = 104). Urinary steroid metabolite excretion was profiled by gas chromatography/mass spectrometry in comparison with healthy controls (n = 88). We found a sharp increase in the excretion of 6β-hydroxycortisol over cortisol (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), indicative of a strong induction of the major drug-metabolizing enzyme cytochrome P450 3A4. The contribution of 6β-hydroxycortisol to total glucocorticoid metabolites increased from 2% (median, interquartile range 1-4%) to 56% (39-71%) during mitotane treatment. Furthermore, we documented strong inhibition of systemic 5α-reductase activity, indicated by a significant decrease in 5α-reduced steroids, including 5α-tetrahydrocortisol, 5α-tetrahydrocorticosterone, and androsterone (all P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The degree of inhibition was similar to that in patients with inactivating 5α-reductase type 2 mutations (n = 23) and patients receiving finasteride (n = 5), but cluster analysis of steroid data revealed a pattern of inhibition distinct from these two groups. Longitudinal data showed rapid onset and long-lasting duration of the observed effects. Cytochrome P450 3A4 induction by mitotane results in rapid inactivation of more than 50% of administered hydrocortisone, explaining the need for doubling hydrocortisone replacement in mitotane-treated patients. Strong inhibition of 5α-reductase activity is in line with the clinical observation of relative inefficiency of testosterone replacement in mitotane-treated men, calling for replacement by 5α-reduced androgens.

Research paper thumbnail of but Has No Effect upon Fat Mass in Patients with Simple Obesity Low-Dose Growth Hormone Inhibits 11ß-Hydroxysteroid Dehydrogenase Type 1

Research paper thumbnail of reductase deficiency

Research paper thumbnail of Expression and Putative Role of 11b-Hydroxysteroid Dehydrogenase Isozymes within the Human Eye

PURPOSE. The human eye is an important target tissue for steroid hormones, and glucocorticoids ha... more PURPOSE. The human eye is an important target tissue for steroid hormones, and glucocorticoids have been implicated in the pathogenesis of ocular disease, including glaucoma. In peripheral tissues, corticosteroid hormone action is regulated at a prereceptor level through the activity of the 11b-hydroxy- steroid dehydrogenase (11b-HSD) isozymes: an oxo-reductase (11b-HSD1) that activates cortisol (F) from cortisone (E) and a dehydrogenase

Research paper thumbnail of Analysis of taxol and related diterpenoids from cell cultures by liquid chromatography-electrospray mass spectrometry

Journal of chromatography, Jan 2, 1993

Authentic taxanes (taxol, 10-deacetyltaxol, cephalomannine, 10-deacetylcephalomannine, baccatin I... more Authentic taxanes (taxol, 10-deacetyltaxol, cephalomannine, 10-deacetylcephalomannine, baccatin III) and extracts from cell cultures derived from various yew tree species have been analyzed by microbore high-performance liquid chromatography (HPLC)-electrospray mass spectrometry (ESMS). All gave excellent positive-ion ES spectra with dominant protonated molecules at low nozzle-to-skimmer bias value (45 V). By increasing the voltage value to 85 V, fragmentation increased and structurally informative spectra were obtained. The fragments found were both of the C-13 side-chain and of the taxane ring, so their analysis gave important information about the taxane structure and any chemical modifications at different positions of the molecule. When tandem MS was used (argon gas, 25 eV collision energy), fragments similar to those obtained from collision-induced dissociation in the source were detected. The cell culture extracts were analyzed by microbore HPLC-ESMS and excellent spectra wer...

Research paper thumbnail of Steroid production and excretion by the pregnant mouse, particularly in relation to pregnancies with fetuses deficient in Δ7-sterol reductase (Dhcr7), the enzyme associated with Smith–Lemli–Opitz syndrome

Research paper thumbnail of Biochemical and physiological improvement in a mouse model of Smith–Lemli–Opitz syndrome (SLOS) following gene transfer with AAV vectors

Molecular Genetics and Metabolism Reports, 2014

Smith-Lemli-Opitz syndrome (SLOS) is an inborn error of cholesterol synthesis resulting from a de... more Smith-Lemli-Opitz syndrome (SLOS) is an inborn error of cholesterol synthesis resulting from a defect in 7-dehydrocholesterol reductase (DHCR7), the enzyme that produces cholesterol from its immediate precursor 7-dehydrocholesterol. Current therapy employing dietary cholesterol is inadequate. As SLOS is caused by a defect in a single gene, restoring enzyme functionality through gene therapy may be a direct approach for treating this debilitating disorder. In the present study, we first packaged a human DHCR7 construct into adeno-associated virus (AAV) vectors having either type-2 (AAV2) or type-8 (AAV2/8) capsid, and administered treatment to juvenile mice. While a positive response (assessed by increases in serum and liver cholesterol) was seen in both groups, the improvement was greater in the AAV2/8-DHCR7 treated mice. Newborn mice were then treated with AAV2/8-DHCR7 and these mice, compared to mice treated as juveniles, showed higher DHCR7 mRNA expression in liver and a greater improvement in serum and liver cholesterol levels. Systemic treatment did not affect brain cholesterol in any of the experimental groups. Both juvenile and newborn treatments with AAV2/8-DHCR7 resulted in increased rates of weight gain indicating that gene transfer had a positive physiological effect.

Research paper thumbnail of Longitudinal changes in glucocorticoid metabolism are associated with later development of adverse metabolic phenotype

European journal of endocrinology / European Federation of Endocrine Societies, 2014

Dysregulation of enzymes that control local tissue steroid metabolism has been implicated in the ... more Dysregulation of enzymes that control local tissue steroid metabolism has been implicated in the pathogenesis of obesity and insulin resistance; however, longitudinal changes in glucocorticoid metabolism have not been investigated. This study was performed to evaluate the role of glucocorticoid metabolism in the development of insulin resistance and obesity and to identify biomarkers for future development of metabolic disease. This was a prospective longitudinal observation study conducted over 5 years. A 24-h collection was used to serially analyze urinary glucocorticoid and mineralocorticoid metabolites in 57 obese and overweight patients with no prior diagnosis of diabetes mellitus, recruited from the community. Baseline higher 5α-reductase (5αR) activity, but not 11β-hydroxysteroid dehydrogenase type 1 activity, was predictive of increased fasting insulin at final visit (11.4 compared with 7.4 mU/l in subjects with lower 5αR activity, P<0.05), area under the curve insulin re...

Research paper thumbnail of Identification of a duplicated P450 side-chain cleavage enzyme (zCyp11a2) defines initiation and maintenance of steroidogenesis in zebrafish

Endocrine Abstracts, 2013

Research paper thumbnail of The zebrafish ferredoxin orthologue Fdx1b is essential for the redox regulation of interrenal steroidogenesis in larvae and adult fish

Endocrine Abstracts, 2013

Research paper thumbnail of Mutants of 11b-Hydroxysteroid Dehydrogenase (11-HSD2) With Partial Activity Improved Correlations Between Genotype and Biochemical Phenotype in Apparent Mineralocorticoid Excess

Mutations in the kidney isozyme of human 11-hydroxysteroid dehydrogenase (11-HSD2) cause apparent... more Mutations in the kidney isozyme of human 11-hydroxysteroid dehydrogenase (11-HSD2) cause apparent mineralocorticoid excess, an autosomal recessive form of familial hypertension. We studied 4 patients with AME, identifying 4 novel and 3 previously reported mutations in the HSD11B2 (HSD11K) gene. Point mutations causing amino acid substitutions were introduced into a pCMV5/11HSD2 expression construct and expressed in mammalian CHOP cells. Mutations

Research paper thumbnail of 232. Gene Therapy for Deficient Cholesterol Synthesis in a Mouse Model of SLOS

Molecular Therapy, 2005

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder, characterized by dysmorphol... more Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder, characterized by dysmorphology and mental retardation. It is a relatively high frequency inherited disease (1:20,000-1:40,000). The cause is a relative inactivity of 7-dehydrocholesterol-Δ7 -reductase (DHCR7), the terminal enzyme in cholesterol (C) synthesis. Affected individuals have low levels of C in blood and tissues and an accumulation of 7-dehydrocholesterol (7-DHC) and its isomer

Research paper thumbnail of Cortisol Metabolism in Human Obesity: Impaired Cortisone3Cortisol Conversion in Subjects with Central Adiposity

For a given body mass index (BMI), mortality is higher in patients with central compared to gener... more For a given body mass index (BMI), mortality is higher in patients with central compared to generalized obesity. Glucocorticoids play an important role in determining body fat distribution, but circulating cortisol concentrations are reported to be normal in obese patients. Our recent studies show enhanced conversion of inactive cortisone (E) to active cortisol (F) through the expression of 11b-hydroxysteroid dehydrogenase

Research paper thumbnail of Confirming testosterone administration by isotope ratio mass spectrometric analysis of urinary androstanediols

Research paper thumbnail of Gas chromatography/mass spectrometry (GC/MS) remains a pre-eminent discovery tool in clinical steroid investigations even in the era of fast liquid chromatography tandem mass spectrometry (LC/MS/MS)

Journal of Steroid Biochemistry and Molecular Biology, 2010

Research paper thumbnail of Quantitation of cortisol and related 3-oxo-4-ene steroids in urine using gas chromatography/mass spectrometry with stable isotope-labeled internal standards

Research paper thumbnail of Comparative Rates of Androgen Production and Metabolism in Caucasian and Chinese Subjects

Clinically apparent prostate cancer occurs more commonly among Caucasians living in Western count... more Clinically apparent prostate cancer occurs more commonly among Caucasians living in Western countries than in Chinese in the Far East. Prior studies demonstrated diminished facial and body hair and lower levels of plasma 3a-androstanediol glucuronide and andros- terone glucuronide in Chinese than in Caucasian men. Based upon these findings, investigators postulated that Chinese men could have diminished 5a-reductase activity with

Research paper thumbnail of A Genetic Defect Resulting in Mild Low-Renin Hypertension

Proceedings of The National Academy of Sciences, 1998

Severe low-renin hypertension has few known causes. Apparent mineralocorticoid excess (AME) is a ... more Severe low-renin hypertension has few known causes. Apparent mineralocorticoid excess (AME) is a genetic disorder that results in severe juvenile low-renin hypertension, hyporeninemia, hypoaldosteronemia, hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. In 1995, it was shown that mutations in the gene (HSD11B2) encoding the 11beta -hydroxysteroid dehydrogenase type 2 enzyme (11beta -HSD2)

Research paper thumbnail of Hair and skin sterols in normal mice and those with deficient dehydrosterol reductase (DHCR7), the enzyme associated with Smith-Lemli-Opitz syndrome

The Journal of Steroid Biochemistry and Molecular Biology, 2010

Research paper thumbnail of Human Δ4-3-oxosteroid 5β-reductase (AKR1D1) deficiency and steroid metabolism